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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 1,117 records · Page 62Linked to original sources
PubMed1988

Brain renin-angiotensin system and the hypothalamic, digitalis-like Na+, K+-ATPase inhibitor in rats.

Since angiotensin (ang) II blockers attenuate the centrally-induced pressor responses to a Na+, K+-ATPase inhibitor, ouabain, a brain renin-ang system is assumed to be involved in this pressor mechanism. Centrally-induced pressor responses to hypertonic saline were also blocked with ang II blockers. Thereby, the increase in the plasma level of digoxin-like immunoreactivity was abolished with simultaneous infusions of an ang II analogue or atrial natriuretic polypeptide (ANP). These results indicate that the pressor responses to sodium salts are mediated via inhibition of the brain Na+, K+-ATPase, and that the brain renin-ang system is involved in this mechanism. We noted the existence of a digoxin-like immunoreactive substance (DLI) containing neurons in the hypothalamus (PVN, SON) with the fibers densely distributed in the AV3V area including OVLT, SFO and the median eminence, an area where receptors for ang II are also distributed (1,2). Since pressor responses to intracerebroventricular (ICV) infusions of hypertonic NaCl are abolished with ICV pretreatment with ang II blockers, a brain renin-ang system may be involved in this mechanism. We then searched for a possible relationship between the central effects of NaCl, a brain renin-ang system and an endogenous Na+, K+-ATPase inhibitor in the hypothalamus.

Animals↗
PubMed1988

The pathophysiological role of water-sodium balance and renal dopaminergic activity in overweight patients with essential hypertension.

Studies were conducted to evaluate the role of water-sodium balance and renal dopaminergic activity in the hypertensive mechanisms of overweight patients with essential hypertension (EHT). The body mass index (BMI) was correlated positively with mean arterial pressure, plasma volume, extracellular fluid volume, or total exchangeable sodium and negatively with plasma noradrenaline concentration or plasma renin activity in patients with EHT. Fractional excretion of sodium (FENa) was significantly lower in overweight patients than in normal weight patients with EHT. Hypotensive effect of sodium restriction or the natriuretic response to infused dopamine was more remarkable in overweight patients with EHT than in normal weight patients with EHT. Urinary excretion of free dopamine (UDA) was correlated positively with simultaneously measured urinary excretion of sodium or FENa and negatively with the natriuretic response to dopamine infusion. In addition, UDA was positively correlated with the BMI in normal weight patients with EHT, whereas the relation between the UDA and the BMI was significantly negative in overweight patients with EHT. These findings suggest that the expansion of body fluid volume and sodium might result from the blunted natriuretic ability due to an attenuation of the renal dopaminergic activity in overweight patients with EHT. The expansion of body fluid volume and sodium may play an important role in the hypertensive mechanisms of overweight patients with EHT.

Adult↗
PubMed1988

Hypothalamic digitalis-like substance is released with sodium-loading in rats.

Role of the hypothalamic digitalis-like substance (EDLS) on the hypertension associated with an excess intake of sodium and the releasing mechanism were investigated. The blood pressure in rats fed with a sodium diet increased significantly after 4 weeks of the treatment compared to the control rats fed with a regular diet, which was accompanied by increased urinary output of the EDLS. Electrical lesions of the AV3V area in the hypothalamus significantly decreased both the urinary EDLS level and the blood pressure elevated by the sodium-loading. With the immunohistochemistry using digoxin antibody, the immunoreactives were localized in the neurons of paraventricular and supraoptic nuclei and some other hypothalamic areas, and were also seen in the nerve fibers distributed in the basal hypothalamus, infundibulum, and pituitary posterior lobe. Assuming that the CSF sodium is responsible for the release of EDLS, hypertonic NaCl (2.5 M) was infused into the lateral ventricle for 30 minutes. Blood pressure increased gradually, attaining peak rises about 30 minutes later. The plasma content of the EDLS was significantly greater in the hypertonic NaCl group than the control group treated with either the artificial CSF or 2.5 M of urea solution. On the other hand, the hypothalamic content decreased with the infusion of the hypertonic saline. Furthermore, the continuous intracerebroventricular infusions of the hypertonic NaCl with osmotic minipumps in conscious rats significantly increased the arterial pressure after 6 days. Thereby, the plasma level of the EDLS was significantly greater than the control rats that received only the artificial CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Endogenous digitalislike substance in an adult population in Japan.

Possible involvement of an endogenous digitalislike substance (EDLS) in blood pressure regulation was investigated using a Japanese population. Mean arterial pressure (MAP) significantly correlated with urinary excretion of the EDLS, age, and the obesity index. The plasma EDLS correlated with urinary EDLS. Urinary EDLS excretion well correlated with the inhibitory activity on Na+,K+-ATPase, and also with the urinary excretion of NaCl. Obesity index correlated with the Na+,K+-ATPase inhibition and arterial pressure. Although plasma content of atrial natriuretic polypeptide correlated with the urinary Na+,K+-ATPase inhibition, it did not correlate with the rest of all parameters. Plasma vasopressin level did not correlate with these parameters either. These results clearly indicate that the circulating EDLS (ie, Na+,K+-ATPase inhibitor) is implicated in the hypertension associated with an excess intake of sodium, aging and obesity.

Adult↗
PubMed1988

Vasopressor responses and hyperthermia by intracerebroventricular injections of penicillin, a pyrogen, in rats: involvement of brain angiotensin II.

Because hypothalamus is a center for both the blood pressure and thermoregulation, we assumed that there is a close interrelationship between them. To prove this hypothesis, effects of intracerebroventricular (ICV) injections of a pyrogen, penicillin-G (Pc), on the blood pressure and rectal temperature (RT) were investigated. The ICV injections increased the mean arterial pressure (MAP), heart rate (HR) and the abdominal sympathetic activity (SNA) dose-dependently in urethane-anesthetized rats. In conscious rats, Pc (100 U) elicited the two components of rises in MAP (+19 +/- 1 and +20 +/- 1 mm Hg), and both the RT and HR increased corresponding to the second phase of MAP responses (+1.0 +/- 0.1 degree C and +60 +/- 7 beats/min). ICV injections of an angiotensin II (ang II) antagonist significantly decreased the MAP (-30 +/- 4 mm Hg), HR (-106 +/- 13 beats/min), and the RT (-0.9 +/- 0.1 degree C). ICV injections of Pc elicited drinking behavior (the vehicle group; 1.1 ml/90 min vs Pc group; 8.6 ml) in rats water-deprivated for 24 hours. In spontaneously hypertensive rats (SHRs), ICV injections of Pc elicited augmented responses in the first phase but diminished in the second pressor phase. ICV injections of an ang II antagonist elicited augmented effects in both the MAP (-39 +/- 1 mm Hg) and RT (-0.8 +/- 0.1 degree C) in SHRs. Thus, RT fluctuated corresponding to the blood pressure level in the latter phase, where a brain ang II mechanism may be involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1988

Digitalis-like substance is produced in the hypothalamus but not in the adrenal gland in rats.

We studied the role of the adrenals on the plasma levels and urinary output of the digoxin-like immunoreactivity in order to elucidate the interrelationship between the adrenals and hypothalamic digoxin-like immunoreactivity. Urine was collected for 24 h 6 days after the bilateral adrenalectomy and then rats were killed by decapitation. Urinary excretion of digoxin-like immunoreactivity did not differ significantly between the sham-operated and adrenalectomized groups, regardless of sodium intake. Plasma levels did not change significantly with sodium-loading, and adrenalectomy did not significantly affect the plasma concentrations of the immunoreactivity. However, bilateral adrenalectomy increased the content of digoxin-like immunoreactivity in the hypothalamus significantly in both rat groups fed with a regular (P less than 0.05) and a high-salt (P less than 0.02) diet. However, when the levels were measured only 16 h after bilateral adrenalectomy, both plasma and hypothalamic contents were significantly higher in the high-salt than the regular-salt group. The correlation between the plasma and hypothalamic content was significant (P less than 0.01). These results strongly suggest that digoxin-like immunoreactivity is produced in the hypothalamus but not in the adrenals, and that the adrenal glands influence the turnover of the hypothalamic endogenous digitalis-like substance.

Adrenal Glands↗
PubMed1988

The effect of ouabain on pressor responses to infused noradrenaline in patients with essential hypertension.

The relationship between changes in the pressor response to infused noradrenaline induced by intravenous injection of ouabain, an Na+,K+-ATPase inhibitor, and plasma renin activity and plasma ionized calcium was examined in 16 normotensive subjects and in 16 patients with essential hypertension. These patients were divided into 11 normal-renin and five low-renin essential hypertensives. The pressor response was significantly greater in low-renin hypertensives than in normotensives and normal-renin hypertensives. Following the injection of ouabain, the pressor response was significantly increased with no change in basal levels of blood pressure, plasma noradrenaline concentration, plasma calcium and plasma parathyroid hormone in both normotensives and essential hypertensives. The pressor response to noradrenaline was negatively correlated with levels of plasma noradrenaline and calcium after the injection of ouabain as well as before the injection in normotensives and essential hypertensives. The regression line between the pressor response and that of plasma noradrenaline or plasma calcium was significantly shifted towards a higher pressor response in normotensives, but not in essential hypertensives. The changes in the pressor response to noradrenaline induced by the injection of ouabain was significantly smaller in essential hypertensives, particularly in low-renin hypertensives, compared with normotensives. These results suggest that: (1) ouabain increases the pressor response to noradrenaline; (2) this increase is related to calcium metabolism; (3) endogenous Na+,K+-ATPase inhibitor(s) might be elevated in essential hypertensives; and (4) an increase in endogenous Na+,K+-ATPase inhibitor might, therefore contribute to an enhanced noradrenaline response in essential hypertensives, particularly in low-renin hypertensives.

Blood Pressure↗
PubMed1988

Zn2+ stimulates spontaneous transmitter release at mouse neuromuscular junctions.

1. Experiments were carried out to examine the effect of Zn2+ on the rate of spontaneous release of transmitter at the neuromuscular junction of the mouse diaphragm muscle, in the presence and absence of external Ca2+. Miniature endplate potentials (m.e.p.ps) were measured in vitro. 2. Zn2+ markedly elevated the frequency of m.e.p.ps without affecting the resting membrane potential of muscle fibres. This effect was time- and concentration-dependent but was independent of the presence of external Ca2+. In a Ca2+-free bathing solution, Zn2+ frequently produced twitching in several fibers. The twitching dislodged the microelectrode. Replacement of the 10 mM NaCl in the Ca2+-free solution with equimolar KCl overcame this difficulty. The experiments summarized below were done in the Ca2+-free bathing solution which contained 10 mM KCl instead of 10 mM NaCl. 3. The effect of Zn2+ was transient and required a latent period of many minutes. Low temperature (24 degrees C) increased the length of this latent period and reduced the maximum effect of Zn2+. 4. Zn2+ increased the frequency of m.e.p.ps in K+-free (replaced with NaCl) solution. The effect appeared with shorter latency in this solution compared to the standard Krebs-Ringer solution. 5. The effect of Zn2+ was partially antagonized by dantrolene sodium or by neomycin. Both agents also reduced the effect of external Ca2+ on m.e.p.ps in depolarizing solution. 6. Cd2+ and 2,3-bisphosphoglycerate also elevated the frequency of m.e.p.ps in a manner independent of external Ca2+, but the latter compound was much less potent than Cd2+. 7. These experiments provide evidence for a role of intracellularly stored Ca24 in the release of transmitter at the motor nerve terminal. The release of Ca24 from the storage site may be coupled with the metabolism of phosphatidylinositol.

Animals↗
PubMed1988

Roles of bacteriochlorophyll and carotenoid synthesis in formation of intracytoplasmic membrane systems and pigment-protein complexes in an aerobic photosynthetic bacterium, Erythrobacter sp. strain OCh114.

Synthesis of bacteriochlorophyll and carotenoids was inhibited in an aerobic photosynthetic bacterium, Erythrobacter sp. strain OCh114, by alpha, alpha'-dipyridyl and diphenylamine. Formation of two pigment-protein complexes, reaction center-B870 (RC-B870) and B806, and development of the intracytoplasmic membranes of the cells were studied by spectral analysis and electron microscopy. Inhibition of bacteriochlorophyll synthesis by alpha, alpha'-dipyridyl, which was accompanied by a decrease in carotenoid synthesis, suppressed formation of intracytoplasmic membranes in the cells. Growth under illumination had a similar effect on formation of pigments and membranes. On the other hand, inhibition of carotenoid synthesis by diphenylamine did not suppress either development of the membrane system or bacteriochlorophyll synthesis. Formation of RC-B870 and B806 complexes, however, was differentially affected by blockage of carotenoid synthesis. In the presence of diphenylamine, the B806 complex was formed in a much smaller amount than the RC-B870 complex. These results suggest that, in Erythrobacter sp. strain OCh114, bacteriochlorophyll plays an essential role in intracytoplasmic membrane development, and carotenoids are important for assembly of pigment-protein complexes.

Aerobiosis↗
PubMed1988

Ionic basis of depressed automaticity and conduction by acetylcholine in rabbit AV node.

To investigate the ionic mechanisms underlying the negative chrono- and dromotropic effects of acetylcholine (ACh) on the atrioventricular (AV) node, experiments were carried out in rabbit AV node preparations with the use of double-microelectrode techniques. In current-clamp experiments (n = 6), 10(-6) M ACh hyperpolarized the resting membrane from -42.3 to -58.2 mV, decreased the specific membrane resistance from 2.54 to 1.27 k omega.cm2, decreased the space constant from 556 to 384 microns, and reduced the membrane time constant from 23.0 to 12.4 ms. Under voltage-clamp conditions, 10(-6) M ACh decreased the slow inward current by 11% and activated an ACh-sensitive outward K+ current (IACh). IACh possessed an inward rectifying property and exhibited a relaxation phenomenon with a time constant of 60-100 ms at a membrane potential of 0 to -80 mV. Its reversal potential varied with a slope factor of 56 mV per 10-fold increase in external K+ concentration. These results suggest that 1) IACh is selective for K+, 2) IACh inhibits phase 4 and phase 0 depolarizations and reduces the space constant for electronic current spread in the AV node, and 3) the negative chrono- and dromotropic actions caused by IACh may be augmented by the ACh-induced reduction in the slow inward current.

Acetylcholine↗
PubMed1988

Effects of inhibitors on chloride outflux from cerebrospinal fluid.

Movement of chloride from cerebrospinal fluid (CSF) to brain or blood is one of the factors that may be involved in regulation of CSF [Cl-], which is important to CSF acid-base balance. We made quantitative measurements of the unidirectional outflux of radiolabeled chloride (38Cl, half-life 37.3 min) from CSF in anesthetized dogs, using ventriculocisternal perfusion (VCP). The outflux of 38Cl from CSF was determined from the difference between the movements of 38Cl and dextran using a one-compartment model. VCP was performed at a rate of 1.4 ml/min for 14 min, and then slowed to 0.28 ml/min. The 38Cl activity decreased to a steady-state level approximately 12% lower than that of dextran within 40-50 min. Under control conditions for the first run (n = 24), the flux was 0.042 +/- 0.003 (SE) ml/min. The outflux under control conditions (n = 6) tended to increase over three separate determinations in a 6-h period, being 136 +/- 19% of the first run on the second run, and 143 +/- 24% on the third. There were no significant changes in 38Cl outflux compared with control ratios after the inclusion of bumetanide in the VCP fluid (n = 6), which inhibits sodium-coupled Cl- transport, with acetazolamide (n = 6), which inhibits carbonic anhydrase, or with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (n = 6), an inhibitor of carrier-mediated anion exchange. These results suggest that the outward movement of chloride from CSF occurs mostly by passive diffusion and is not by mediated transport.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1988

Assessment of warfarin therapy under full dose using indium-111 platelet scintigraphy in patients with intracardiac thrombi.

Twenty patients in whom intracardiac thrombi were detected by indium-111 platelet scintigraphy (the first platelet scintigraphy) were prospectively studied to examine the effect of warfarin therapy under full dose on the intracardiac thrombogenicity. Eleven patients (group I) who received 2-6 mg/day of warfarin and 9 patients (group II) who did not receive warfarin had the second platelet scintigraphies 14-71 days after the first platelet scintigraphies. In group I, 10 platelet scintigraphies became negative and one remained positive for intracardiac thrombi after administration of warfarin, while in group II 8 platelet scintigraphies remained positive and only one changed to negative. The incidence of negative image at the second platelet scintigraphy was significantly lower in group II than that in group I. In group I, the degree of accumulation of platelets onto the surface of the thrombus (%IE), showed significant reduction (0.69 +/- 0.48 to 0.11 +/- 0.21) after warfarin therapy, while in group II %IE at the second scintigraphy (1.07 +/- 1.03) were not significantly different from those at the first scintigraphy (1.13 +/- 0.79). These results indicated that warfarin therapy under full dose inhibited the deposition of platelets on the intracardiac thrombi and thrombogenicity in the patients with intracardiac thrombi which were detected by indium-111 platelet scintigraphy.

Adult↗
PubMed1988

Influence of B-cell impairment on pancreatic acini in NOD mice and streptozotocin-induced diabetic rats.

Exocrine pancreatic function insufficiency, even of short duration, has been reported in juvenile-onset insulin dependent diabetic patients. To evaluate the status of pancreatic acini under decreased B-cell function, tissue insulin, amylase, chymotrypsinogen and trypsinogen in the pancreas were measured in streptozotocin-induced diabetic rats and non-obese diabetic mice in various conditions. In streptozotocin diabetic rats, a dissociation of three enzyme contents was demonstrated in the condition with discontinuation of insulin injection, i.e., a marked decrease in amylase, a significant increase in chymotrypsinogen, but no significant change in trypsinogen. This dissociation was markedly improved in the insulin-treated condition. In non-obese diabetic mice, these enzyme contents were not significantly changed although severe insulitis together with the marked decrease in insulin content was observed. These data show that the cessation of B-cell function alone does not cause insufficiency of exocrine pancreas.

Amylases↗
PubMed1988

A case-control study of lung cancer in nonsmoking women.

A case-control study of Japanese women in Nagoya was conducted to investigate the significance of passive smoking and other factors in relation to the etiology of female lung cancer. A total of 90 nonsmoking patients with primary lung cancer and their age- and hospital-matched female controls were asked to fill in a questionnaire in the hospital. Elevated relative risk (RR) of lung cancer was observed for passive smoking from mother (RR = 4.0; p less than 0.05) and from husband's father (RR = 3.2; p less than 0.05). No association was observed between the risk of lung cancer and smoking of husband or passive smoke exposure at work. Occupational exposure to iron or other metals also showed high risk (RR = 4.8; p less than 0.05). No appreciable differences in food intakes were observed between cases and controls.

Adult↗